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Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2016 (English)In: Biomolecules, ISSN 0045-2068, E-ISSN 2218-273X, Vol. 6, no 3, 38Article in journal (Refereed) Published
Abstract [en]

There is a need to identify novel scaffolds and targets to develop new antibiotics. Methylene blue is a phenothiazine derivative, and it has been shown to possess anti-malarial and anti-trypanosomal activities. Here, we show that different phenothiazine derivatives and pyronine G inhibited the activities of three structurally different bacterial RNase P RNAs (RPRs), including that from Mycobacterium tuberculosis, with K-i values in the lower mu M range. Interestingly, three antipsychotic phenothiazines (chlorpromazine, thioridazine, and trifluoperazine), which are known to have antibacterial activities, also inhibited the activity of bacterial RPRs, albeit with higher Ki values than methylene blue. Phenothiazines also affected lead(II)-induced cleavage of bacterial RPR and inhibited yeast tRNAPhe, indicating binding of these drugs to functionally important regions. Collectively, our findings provide the first experimental data showing that long, noncoding RNAs could be targeted by different phenothiazine derivatives.

Place, publisher, year, edition, pages
2016. Vol. 6, no 3, 38
Keyword [en]
RNA processing, catalytic RNA, RNase P, phenothiazines
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-304162DOI: 10.3390/biom6030038ISI: 000382578800010OAI: oai:DiVA.org:uu-304162DiVA: diva2:1014905
Available from: 2016-10-03 Created: 2016-10-03 Last updated: 2017-11-30Bibliographically approved

Open Access in DiVA

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